Basic mechanisms and influences upon ischemic myocardial dysfunction and the development of tissue injury and infarction will be investigated. Isolated buffer and blood perfused rabbit hearts will be used to study the metabolic, structural and functional changes which occur during a 90-180 minute period of moderate or severe ischemia, a time period which embraces the transition from reversible to irreversible injury. The degree of ischemia which exists in the central and border zones of an infarction will be modelled to investigate: 1) The effects of global ischemia of different degrees of severity and duration, 2) The separate components of the ischemic injury process (coronary arterial pressure, flow and oxygen delivery reduction, "paradoxical" systolic stretch, ischemic contracture, glycolysis, contactile work and metabolic demand, calcium accumulation, edema, substrate type (glucose, vs. free fatty acid), phosphate and adenosine leakage, autolysis, reduced redox state, acidosis, and reperfusion), 3) Consequences of "primary" ischemia in comparison to "relative" ischemia, and 4) Post-ischemic depression of cardiac fuction.